Field of the Invention
The present invention relates to methods, devices, and systems for fluid mixing and providing fluid to microfluidic devices. More particularly, aspects of the present invention relate to methods, devices, and systems for mixing fluids and delivering them into a microfluidic interface chip, and creating fluid segments that move through a microfluidic chip with minimal mixing between segments.
Description of the Background
In the field of microfluidics, a miniaturized total analysis system (μ-TAS), such as a “lab-on-a-chip,” is frequently used for chemical sensing. A μ-TAS integrates many of the steps performed in chemical analysis—steps such as sampling, pre-processing, and measurement—into a single miniaturized device, resulting in improved selectivity and detection limit(s) compared to conventional sensors. Structures for performing common analytical assays, including polymerase chain reaction (PCR), deoxyribonucleic nucleic acid (DNA) analyses, protein separations, immunoassays, and intra- and inter-cellular analysis, are reduced in size and fabricated in a centimeter-scale chip. The reduction in the size of the structures for performing such analytical processes has many advantages including more rapid analysis, less sample amount required for each analysis, and smaller overall instrumentation size.
One of the advantages of lab-on-a-chip systems is the potential for mixing of reagents to occur on the chip. However, since laminar flow is the dominant flow mode in microfluidic systems, it is difficult to fully mix fluids in continuous flow systems. Fully mixed fluids can be achieved by, for example, increasing the time for mixing by diffusion. This can be achieved by increasing the channel length, slowing the flow rate, etc. Structures that disrupt laminar flow can also be introduced in the channel. See, e.g., U.S. Patent Application Publication No. 2010/0067323 to Blom et al. In a continuous flow system, however, increasing the degree of mixing of laminated fluids within a fluid sample (i.e., a droplet, slug, or plug of analyte or blanking fluid) also causes increased mixing between fluids in the series of fluid segments moving through the channel. That is, approaches which increase the on-chip or in-channel intermixing of fluids within a sample will also tend to increase the intramixing of fluids between samples. Thus, the length of the segments of fluids moving through the chip must be large enough such that mixing at the interface or boundary between the segments does not affect the analytical result.
Another issue with current μ-TASs and other microfluidic devices is the connection between the macro-environment of the world outside the device and the micro-components of a device. This aspect of the device is often referred to as the macro-to-micro interface, interconnect, or world-to-chip interface. The difficulty results from the fact that samples and reagents are typically transferred in quantities of microliters (μL) to milliliters (mL) whereas microfluidic devices typically consume only nanoliters (nL) or picoliters (pL) of samples or reagents due to the size of reaction chambers and channels, which typically have dimensions on the order of micrometers.
One method for introducing fluids into a microfluidic system is to simply form a well on the microfluidic device that connects directly to the microfluidic channel and place liquid in the well using a macrofluidic pipetting device. See, e.g., U.S. Pat. No. 5,858,195 to Ramsey and U.S. Pat. No. 5,955,028 to Chow. One disadvantage of this method is that it does not easily allow for a series of different fluids to be introduced into the same channel. This can reduce the efficacy of high throughput or continuous flow devices.
Another method for introducing fluids into a microfluidic system includes the use of a capillary (known in the art as a “sipper”) attached directly to the chip that can be used to draw liquids into the chip. See, e.g., U.S. Pat. No. 6,150,180 to Parce et al. This method allows for different liquids to be drawn into the same channel in serial fashion. A disadvantage of this method is that air can also be drawn into the sipper which blocks the flow of liquid. Furthermore, the length of the column of liquid in the sipper adds a hydrostatic pressure that must be overcome to draw liquid into the chip. Keeping the pressure balanced so that flow is produced without drawing air into the sipper complicates the device design.
Accordingly, there is a need for providing improved methods, devices, and systems for fluid mixing and providing fluid to microfluidic devices.